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Indian Journal of Pediatrics Dec 2001Acute respiratory infections accounts for 20-40% of outpatient and 12-35% of inpatient attendance in a general hospital. Upper respiratory tract infections including... (Review)
Review
Acute respiratory infections accounts for 20-40% of outpatient and 12-35% of inpatient attendance in a general hospital. Upper respiratory tract infections including nasopharyngitis, pharyngitis, tonsillitis and otitis media constitute 87.5% of the total episodes of respiratory infections. The vast majority of acute upper respiratory tract infections are caused by viruses. Common cold is caused by viruses in most circumstances and does not require antimicrobial agent unless it is complicated by acute otitis media with effusion, tonsillitis, sinusitis, and lower respiratory tract infection. Sinusitis is commonly associated with common cold. Most instances of rhinosinusitis are viral and therefore, resolve spontaneously without antimicrobial therapy. The most common bacterial agents causing sinusitis are S. pneumoniae, H. influenzae, M. catarrhalis, S. aureus and S. pyogenes. Amoxycillin is antibacterial of choice. The alternative drugs are cefaclor or cephalexin. The latter becomes first line if sinusitis is recurrent or chronic. Acute pharyngitis is commonly caused by viruses and does not need antibiotics. About 15% of the episodes may be due to Group A beta hemolytic streptococcus (GABS). Early initiation of antibiotics in pharyngitis due to GABS can prevent complications such as acute rheumatic fever. The drug of choice is penicillin for 10-14 days. The alternative medications include oral cephalosporins (cefaclor, cephalexin), amoxicillin or macrolides.
Topics: Anti-Bacterial Agents; Child; Common Cold; Humans; India; Pharyngitis; Respiratory Tract Infections; Sinusitis
PubMed: 11838568
DOI: 10.1007/BF02722930 -
American Family Physician Oct 2011Urinary tract infections are the most common bacterial infections in women. Most urinary tract infections are acute uncomplicated cystitis. Identifiers of acute... (Review)
Review
Urinary tract infections are the most common bacterial infections in women. Most urinary tract infections are acute uncomplicated cystitis. Identifiers of acute uncomplicated cystitis are frequency and dysuria in an immunocompetent woman of childbearing age who has no comorbidities or urologic abnormalities. Physical examination is typically normal or positive for suprapubic tenderness. A urinalysis, but not urine culture, is recommended in making the diagnosis. Guidelines recommend three options for first-line treatment of acute uncomplicated cystitis: fosfomycin, nitrofurantoin, and trimethoprim/sulfamethoxazole (in regions where the prevalence of Escherichia coli resistance does not exceed 20 percent). Beta-lactam antibiotics, amoxicillin/clavulanate, cefaclor, cefdinir, and cefpodoxime are not recommended for initial treatment because of concerns about resistance. Urine cultures are recommended in women with suspected pyelonephritis, women with symptoms that do not resolve or that recur within two to four weeks after completing treatment, and women who present with atypical symptoms.
Topics: Anti-Bacterial Agents; Cystitis; Dysuria; Female; Humans; Urinalysis
PubMed: 22010614
DOI: No ID Found -
Otolaryngology--head and Neck Surgery :... Jan 2004Treatment guidelines developed by the Sinus and Allergy Health Partnership for acute bacterial rhinosinusitis (ABRS) were originally published in 2000. These guidelines... (Review)
Review
UNLABELLED
Treatment guidelines developed by the Sinus and Allergy Health Partnership for acute bacterial rhinosinusitis (ABRS) were originally published in 2000. These guidelines were designed to: (1) educate clinicians and patients (or patients’ families) about the differences between viral and bacterial rhinosinusitis; (2) reduce the use of antibiotics for nonbacterial nasal/sinus disease; (3) provide recommendations for the diagnosis and optimal treatment of ABRS; (4) promote the use of appropriate antibiotic therapy when bacterial infection is likely; and (5) describe the current understanding of pharmacokinetic and pharmacodynamics and how they relate to the effectiveness of antimicrobial therapy. The original guidelines are updated here to include the most recent information on management principles, antimicrobial susceptibility patterns, and therapeutic options.
BURDEN OF DISEASE
An estimated 20 million cases of ABRS occur annually in the United States. According to National Ambulatory Medical Care Survey (NAMCS) data, sinusitis is the fifth most common diagnosis for which an antibiotic is prescribed. Sinusitis accounted for 9% and 21% of all pediatric and adult antibiotic prescriptions, respectively, written in 2002. The primary diagnosis of sinusitis results in expenditures of approximately $3.5 billion per year in the United States.
DEFINITION AND DIAGNOSIS OF ABRS
ABRS is most often preceded by a viral upper respiratory tract infection (URI). Allergy, trauma, dental infection, or other factors that lead to inflammation of the nose and paranasal sinuses may also predispose individuals to developing ABRS. Patients with a “common cold” (viral URI) usually report some combination of the following symptoms: sneezing, rhinorrhea, nasal congestion, hyposmia/anosmia, facial pressure, postnasal drip, sore throat, cough, ear fullness, fever, and myalgia. A change in the color or the characteristic of the nasal discharge is not a specific sign of a bacterial infection. Bacterial superinfection may occur at any time during the course of a viral URI. The risk that bacterial superinfection has occurred is greater if the illness is still present after 10 days. Because there may be cases that fall out of the “norm” of this typical progression, practicing clinicians need to rely on their clinical judgment when using these guidelines. In general, however, a diagnosis of ABRS may be made in adults or children with symptoms of a viral URI that have not improved after 10 days or worsen after 5 to 7 days. There may be some or all of the following signs and symptoms: nasal drainage, nasal congestion, facial pressure/pain (especially when unilateral and focused in the region of a particular sinus), postnasal drainage, hyposmia/anosmia, fever, cough, fatigue, maxillary dental pain, and ear pressure/fullness. Physical examination provides limited information in the diagnosis of ABRS. While sometimes helpful, plain film radiographs, computed tomography (CT), and magnetic resonance imaging scans are not necessary for cases of ABRS.
MICROBIOLOGY OF ABRS
The most common bacterial species isolated from the maxillary sinuses of patients with ABRS are , , and , the latter being more common in children. Other streptococcal species, anaerobic bacteria and cause a small percentage of cases.
BACTERIAL RESISTANCE IN ABRS
The increasing prevalence of penicillin nonsusceptibility and resistance to other drug classes among has been a problem in the United States, with 15% being penicillin-intermediate and 25% being penicillin-resistant in recent studies. Resistance to macrolides and trimethoprim/sulfamethoxazole (TMP/SMX) is also common in . The prevalence of β-lactamase-producing isolates of is approximately 30%, while essentially all isolates produce β-lactamases. Resistance of to TMP/SMX is also common.
ANTIMICROBIAL TREATMENT GUIDELINES FOR ABRS
These guidelines apply to both adults and children. When selecting antibiotic therapy for ABRS, the clinician should consider the severity of the disease, the rate of progression of the disease, and recent antibiotic exposure. The guidelines now divide patients with ABRS into two general categories: (1) those with mild symptoms who have not received antibiotics within the past 4 to 6 weeks, and (2) those with mild disease who have received antibiotics within the past 4 to 6 weeks or those with moderate disease regardless of recent antibiotic exposure. The difference in severity of disease does not imply infection with a resistant pathogen. Rather, this terminology indicates the relative degree of acceptance of possible treatment failure and the likelihood of spontaneous resolution of symptoms—patients with more severe symptoms are less likely to resolve their disease spontaneously. The primary goal of antibiotic therapy is to eradicate bacteria from the site of infection, which, in turn, helps (1) return the sinuses back to health; (2) decrease the duration of symptoms to allow patients to resume daily activities more quickly; (3) prevent severe complications such as meningitis and brain abscess; and (4) decrease the development of chronic disease. Severe or life-threatening infections with or without complications are rare, and are not addressed in these guidelines. Prior antibiotic use is a major risk factor associated with the development of infection with antimicrobial-resistant strains. Because recent antimicrobial exposure increases the risk of carriage of and infection due to resistant organisms, antimicrobial therapy should be based upon the patient’s history of recent antibiotic use. The panel’s guidelines, therefore, stratify patients according to antibiotic exposure in the previous 4 to 6 weeks. Lack of response to therapy at ≥72 hours is an arbitrary time established to define treatment failures. Clinicians should monitor the response to antibiotic therapy, which may include instructing the patient to call the office or clinic if symptoms persist or worsen over the next few days. The predicted bacteriologic and clinical efficacy of antibiotics in adults and children has been determined according to mathematical modeling of ABRS developed by Michael Poole, MD, PhD, based on pathogen distribution, resolution rates without treatment, and in vitro microbiologic activity. Antibiotics can be placed into the following relative rank order of predicted clinical efficacy for adults: 90% to 92% = respiratory fluoroquinolones (gatifloxacin, levofloxacin, moxifloxacin), ceftriaxone, high-dose amoxicillin/clavulanate (4 g/250 mg/day), and amoxicillin/clavulanate (1.75 g/250 mg/day); 83% to 88% = high-dose amoxicillin (4 g/day), amoxicillin (1.5 g/day), cefpodoxime proxetil, cefixime (based on and coverage), cefuroxime axetil, cefdinir, and TMP/SMX; 77% to 81% = doxycycline, clindamycin (based on gram-positive coverage only), azithromycin, clarithromycin and erythromycin, and telithromycin; 65% to 66% = cefaclor and loracarbef. The predicted spontaneous resolution rate in patients with a clinical diagnosis of ABRS is 62%. Antibiotics can be placed into the following relative rank order of predicted clinical efficacy in children with ABRS: 91% to 92% = ceftriaxone, high-dose amoxicillin/clavulanate (90 mg/6.4 mg per kg per day) and amoxicillin/clavulanate (45 mg/6.4 mg per kg per day); 82% to 87% = high-dose amoxicillin (90 mg/kg per day), amoxicillin (45 mg/kg per day), cefpodoxime proxetil, cefixime (based on and coverage only), cefuroxime axetil, cefdinir, and TMP/SMX; and 78% to 80% = clindamycin (based on gram-positive coverage only), cefprozil, azithromycin, clarithromycin, and erythromycin; 67% to 68% = cefaclor and loracarbef. The predicted spontaneous resolution rate in untreated children with a presumed diagnosis of ABRS is 63%. Recommendations for initial therapy for adult patients with mild disease (who have not received antibiotics in the previous 4 to 6 weeks) include the following choices: amoxicillin/clavulanate (1.75 to 4 g/250 mg per day), amoxicillin (1.5 to 4 g/day), cefpodoxime proxetil, cefuroxime axetil, or cefdinir. While TMP/SMX, doxycycline, azithromycin, clarithromycin, erythromycin, or telithromycin may be considered for patients with β-lactam allergies, bacteriologic failure rates of 20% to 25% are possible. Failure to respond to antimicrobial therapy after 72 hours should prompt either a switch to alternate antimicrobial therapy or reevaluation of the patient (see Table 4).When a change in antibiotic therapy is made, the clinician should consider the limitations in coverage of the initial agent. Recommendations for initial therapy for adults with mild disease who have received antibiotics in the previous 4 to 6 weeks adults with moderate disease include the following choices: respiratory fluoroquinolone (eg, gatifloxacin, levofloxacin, moxifloxacin) or high-dose amoxicillin/clavulanate (4 g/250 mg per day). The widespread use of respiratory fluoroquinolones for patients with milder disease may promote resistance of a wide spectrum of organisms to this class of agents. Ceftriaxone (parenteral, 1 to 2 g/day for 5 days) or combination therapy with adequate gram-positive and negative coverage may also be considered. Examples of appropriate regimens of combination therapy include high-dose amoxicillin or clindamycin plus cefixime, or high-dose amoxicillin or clindamycin plus rifampin. While the clinical effectiveness of ceftriaxone and these combinations for ABRS is unproven; the panel considers these reasonable therapeutic options based on the spectrum of activity of these agents and on data extrapolated from acute otitis media studies. Rifampin should not be used as monotherapy, casually, or for longer than 10 to 14 days, as resistance quickly develops to this agent. Rifampin is also a well-known inducer of several cytochrome p450 isoenzymes and therefore has a high potential for drug interactions. Failure of a patient to respond to antimicrobial therapy after 72 hours of therapy should prompt either a switch to alternate antimicrobial therapy or reevaluation of the patient (see Table 4). When a change in antibiotic therapy is made, the clinician should consider the limitations in coverage of the initial agent. Patients who have received effective antibiotic therapy and continue to be symptomatic may need further evaluation. A CT scan, fiberoptic endoscopy or sinus aspiration and culture may be necessary. Recommendations for initial therapy for children with disease and who have received antibiotics in the previous 4 to 6 weeks include the following: high-dose amoxicillin/clavulanate (90 mg/6.4 mg per kg per day), amoxicillin (90 mg/kg per day), cefpodoxime proxetil, cefuroxime axetil, or cefdinir. TMP/SMX, azithromycin, clarithromycin, or erythromycin is recommended if the patient has a history of immediate Type I hypersensitivity reaction to β-lactams. These antibiotics have limited effectiveness against the major pathogens of ABRS and bacterial failure of 20% to 25% is possible. The clinician should differentiate an immediate hypersensitivity reaction from other less dangerous side effects. Children with immediate hypersensitivity reactions to β-lactams may need: desensitization, sinus cultures, or other ancillary procedures and studies. Children with other types of reactions and side effects may tolerate one specific β-lactam, but not another. Failure to respond to antimicrobial therapy after 72 hours should prompt either a switch to alternate antimicrobial therapy or reevaluation of the patient (see Table 5).When a change in antibiotic therapy is made, the clinician should consider the limitations in coverage of the initial agent. The recommended initial therapy for children with disease who received antibiotics in the previous 4 to 6 weeks children with disease is high-dose amoxicillin/clavulanate (90 mg/6.4 mg per kg per day). Cefpodoxime proxetil, cefuroxime axetil, or cefdinir may be used if there is a penicillin allergy (eg, penicillin rash); in such instances, cefdinir is preferred because of high patient acceptance. TMP/SMX, azithromycin, clarithromycin, or erythromycin is recommended if the patient is β-lactam allergic, but these do not provide optimal coverage. Clindamycin is appropriate if is identified as a pathogen. Ceftriaxone (parenteral, 50 mg/kg per day for 5 days) or combination therapy with adequate gram-positive and -negative coverage may also be considered. Examples of appropriate regimens of combination therapy include high-dose amoxicillin or clindamycin plus cefixime, or high-dose amoxicillin or clindamycin plus rifampin. The clinical effectiveness of ceftriaxone and these combinations for ABRS is unproven; the panel considers these reasonable therapeutic options based on spectrum of activity and on data extrapolated from acute otitis media studies. Rifampin should not be used as monotherapy, casually, or for longer than 10 to 14 days as resistance quickly develops to this agent. Failure to respond to antimicrobial therapy after 72 hours of therapy should prompt either a switch to alternate antimicrobial therapy or reevaluation of the patient (see Table 5). When a change in antibiotic therapy is made, the clinician should consider the limitations in coverage of the initial agent. Patients who have received effective antibiotic therapy and continue to be symptomatic may need further evaluation. A CT scan, fiberoptic endoscopy or sinus aspiration and culture may be necessary.
Topics: Acute Disease; Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Bacterial; Drug Therapy, Combination; Fluoroquinolones; Haemophilus influenzae; Humans; Lactams; Macrolides; Microbial Sensitivity Tests; Monte Carlo Method; Moraxella catarrhalis; Nasopharynx; Otitis Media; Rhinitis; Sinusitis; Streptococcus pneumoniae
PubMed: 14726904
DOI: 10.1016/j.otohns.2003.12.003 -
The Journal of Allergy and Clinical... Aug 2020
Topics: Cefaclor; Epitopes; Humans; Immunoglobulin E
PubMed: 32362530
DOI: 10.1016/j.jaci.2020.03.023 -
The Cochrane Database of Systematic... Feb 2021Bacterial folliculitis and boils are globally prevalent bacterial infections involving inflammation of the hair follicle and the perifollicular tissue. Some... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bacterial folliculitis and boils are globally prevalent bacterial infections involving inflammation of the hair follicle and the perifollicular tissue. Some folliculitis may resolve spontaneously, but others may progress to boils without treatment. Boils, also known as furuncles, involve adjacent tissue and may progress to cellulitis or lymphadenitis. A systematic review of the best evidence on the available treatments was needed.
OBJECTIVES
To assess the effects of interventions (such as topical antibiotics, topical antiseptic agents, systemic antibiotics, phototherapy, and incision and drainage) for people with bacterial folliculitis and boils.
SEARCH METHODS
We searched the following databases up to June 2020: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We also searched five trials registers up to June 2020. We checked the reference lists of included studies and relevant reviews for further relevant trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that assessed systemic antibiotics; topical antibiotics; topical antiseptics, such as topical benzoyl peroxide; phototherapy; and surgical interventions in participants with bacterial folliculitis or boils. Eligible comparators were active intervention, placebo, or no treatment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Our primary outcomes were 'clinical cure' and 'severe adverse events leading to withdrawal of treatment'; secondary outcomes were 'quality of life', 'recurrence of folliculitis or boil following completion of treatment', and 'minor adverse events not leading to withdrawal of treatment'. We used GRADE to assess the certainty of the evidence.
MAIN RESULTS
We included 18 RCTs (1300 participants). The studies included more males (332) than females (221), although not all studies reported these data. Seventeen trials were conducted in hospitals, and one was conducted in clinics. The participants included both children and adults (0 to 99 years). The studies did not describe severity in detail; of the 232 participants with folliculitis, 36% were chronic. At least 61% of participants had furuncles or boils, of which at least 47% were incised. Duration of oral and topical treatments ranged from 3 days to 6 weeks, with duration of follow-up ranging from 3 days to 6 months. The study sites included Asia, Europe, and America. Only three trials reported funding, with two funded by industry. Ten studies were at high risk of 'performance bias', five at high risk of 'reporting bias', and three at high risk of 'detection bias'. We did not identify any RCTs comparing topical antibiotics against topical antiseptics, topical antibiotics against systemic antibiotics, or phototherapy against sham light. Eleven trials compared different oral antibiotics. We are uncertain as to whether cefadroxil compared to flucloxacillin (17/21 versus 18/20, risk ratio (RR) 0.90, 95% confidence interval (CI) 0.70 to 1.16; 41 participants; 1 study; 10 days of treatment) or azithromycin compared to cefaclor (8/15 versus 10/16, RR 1.01, 95% CI 0.72 to 1.40; 31 participants; 2 studies; 7 days of treatment) differed in clinical cure (both very low-certainty evidence). There may be little to no difference in clinical cure rate between cefdinir and cefalexin after 17 to 24 days (25/32 versus 32/42, RR 1.00, 95% CI 0.73 to 1.38; 74 participants; 1 study; low-certainty evidence), and there probably is little to no difference in clinical cure rate between cefditoren pivoxil and cefaclor after 7 days (24/46 versus 21/47, RR 1.17, 95% CI 0.77 to 1.78; 93 participants; 1 study; moderate-certainty evidence). For risk of severe adverse events leading to treatment withdrawal, there may be little to no difference between cefdinir versus cefalexin after 17 to 24 days (1/191 versus 1/200, RR 1.05, 95% CI 0.07 to 16.62; 391 participants; 1 study; low-certainty evidence). There may be an increased risk with cefadroxil compared with flucloxacillin after 10 days (6/327 versus 2/324, RR 2.97, 95% CI 0.60 to 14.62; 651 participants; 1 study; low-certainty evidence) and cefditoren pivoxil compared with cefaclor after 7 days (2/77 versus 0/73, RR 4.74, 95% CI 0.23 to 97.17; 150 participants; 1 study; low-certainty evidence). However, for these three comparisons the 95% CI is very wide and includes the possibility of both increased and reduced risk of events. We are uncertain whether azithromycin affects the risk of severe adverse events leading to withdrawal of treatment compared to cefaclor (274 participants; 2 studies; very low-certainty evidence) as no events occurred in either group after seven days. For risk of minor adverse events, there is probably little to no difference between the following comparisons: cefadroxil versus flucloxacillin after 10 days (91/327 versus 116/324, RR 0.78, 95% CI 0.62 to 0.98; 651 participants; 1 study; moderate-certainty evidence) or cefditoren pivoxil versus cefaclor after 7 days (8/77 versus 5/73, RR 1.52, 95% CI 0.52 to 4.42; 150 participants; 1 study; moderate-certainty evidence). We are uncertain of the effect of azithromycin versus cefaclor after seven days due to very low-certainty evidence (7/148 versus 4/126, RR 1.26, 95% CI 0.38 to 4.17; 274 participants; 2 studies). The study comparing cefdinir versus cefalexin did not report data for total minor adverse events, but both groups experienced diarrhoea, nausea, and vaginal mycosis during 17 to 24 days of treatment. Additional adverse events reported in the other included studies were vomiting, rashes, and gastrointestinal symptoms such as stomach ache, with some events leading to study withdrawal. Three included studies assessed recurrence following completion of treatment, none of which evaluated our key comparisons, and no studies assessed quality of life.
AUTHORS' CONCLUSIONS
We found no RCTs regarding the efficacy and safety of topical antibiotics versus antiseptics, topical versus systemic antibiotics, or phototherapy versus sham light for treating bacterial folliculitis or boils. Comparative trials have not identified important differences in efficacy or safety outcomes between different oral antibiotics for treating bacterial folliculitis or boils. Most of the included studies assessed participants with skin and soft tissue infection which included many disease types, whilst others focused specifically on folliculitis or boils. Antibiotic sensitivity data for causative organisms were often not reported. Future trials should incorporate culture and sensitivity information and consider comparing topical antibiotic with antiseptic, and topical versus systemic antibiotics or phototherapy.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Infective Agents, Local; Bias; Carbuncle; Child; Child, Preschool; Female; Furunculosis; Humans; Infant; Infant, Newborn; Male; Middle Aged; Randomized Controlled Trials as Topic; Young Adult
PubMed: 33634465
DOI: 10.1002/14651858.CD013099.pub2 -
Journal of Global Antimicrobial... Mar 2020The aim of this study was to describe antibiotic prescribing patterns and antimicrobial resistance rates in hospitalised children with febrile and afebrile urinary tract...
OBJECTIVES
The aim of this study was to describe antibiotic prescribing patterns and antimicrobial resistance rates in hospitalised children with febrile and afebrile urinary tract infections (UTIs).
METHODS
Antibiotic prescriptions and antibiograms for neonates, infants and older children with UTI admitted to a general district hospital in Central Greece were evaluated. Data covering a 5-year period were collected retrospectively from the Paediatric Department's Electronic Clinical Archive. Patients were included based on clinical and microbiological criteria. Antimicrobial susceptibility was determined by the Kirby-Bauer disk diffusion method.
RESULTS
A total of 230 patients were included in the study. Among 459 prescriptions identified, amikacin (31.2%) was the most common antibiotic prescribed in this population, followed by amoxicillin/clavulanic acid (17.4%) and ampicillin (13.5%). Children received prolonged intravenous (i.v.) treatments for febrile (mean ± S.D., 5.4 ± 1.45 days) and afebrile UTIs (mean ± S.D., 4.4 ± 1.64 days). A total of 236 pathogens were isolated. The main causative organism was Escherichia coli (79.2%) with high reported resistance rates to ampicillin (42.0%), trimethoprim/sulfamethoxazole (26.5%) and amoxicillin/clavulanic acid (12.2%); lower resistance rates were identified for third-generation cephalosporins (1.7%), nitrofurantoin (2.3%), ciprofloxacin (1.4%) and amikacin (0.9%). Klebsiella spp. isolates were highly resistant to cefaclor (27.3%).
CONCLUSION
High prescribing rates for amikacin and penicillins (± β-lactamase inhibitors) and prolonged i.v. treatments were observed. Escherichia coli was highly resistant to ampicillin, whilst third-generation cephalosporins exhibited greater in vitro efficacy. Establishment of antimicrobial stewardship programmes and regular monitoring of antimicrobial resistance could help to minimise inappropriate prescribing for UTIs.
Topics: Administration, Intravenous; Adolescent; Amikacin; Amoxicillin-Potassium Clavulanate Combination; Ampicillin; Anti-Bacterial Agents; Antimicrobial Stewardship; Child; Child, Preschool; Disk Diffusion Antimicrobial Tests; Drug Resistance, Multiple, Bacterial; Escherichia coli; Female; Fever; Greece; Humans; Infant; Infant, Newborn; Klebsiella; Male; Retrospective Studies; Urinary Tract Infections
PubMed: 31252156
DOI: 10.1016/j.jgar.2019.06.016 -
Scientific Reports Sep 2023Antibiotics are increasingly recognized as causing neuropsychiatric side effects including depression and anxiety. Alterations in central serotonin and 5-HT receptor...
Antibiotics are increasingly recognized as causing neuropsychiatric side effects including depression and anxiety. Alterations in central serotonin and 5-HT receptor expression are implicated in the pathogenesis of anxiety and depression, which are highly comorbid with gastrointestinal disorders. Nevertheless, it is still unclear how antibiotics can cause anxiety and depression. In this study, oral administration of cefaclor, a second-generation cephalosporin antibiotic, induced anxiety- and depression-like behaviors and colitis with gut microbiota alteration in mice. Cefaclor reduced serotonin levels and fluctuated 5-HT receptor mRNA expressions such as Htr1a, Htr1b, and Htr6 in the hippocampus. Vagotomy attenuated the cefaclor-induced anxiety- and depression-like symptoms, while the cefaclor-induced changes in gut bacteria alteration and colitis were not affected. Fluoxetine attenuated cefaclor-induced anxiety- and depression-like behaviors. Furthermore, fluoxetine decreased cefaclor-resistant Enterobacteriaceae and Enterococcaceae. Taken together, our findings suggest that the use of antibiotics, particularly, cefaclor may cause gut dysbiosis-dependent anxiety and depression through the microbiota-gut-blood-brain and microbiota-gut-vagus nerve-brain pathway. Targeting antibiotics-resistant pathogenic bacteria may be a promising therapeutic strategy for the treatment of anxiety and depression.
Topics: Animals; Mice; Cefaclor; Depression; Dysbiosis; Fluoxetine; Serotonin; Anti-Bacterial Agents; Vagus Nerve; Colitis
PubMed: 37726354
DOI: 10.1038/s41598-023-42690-1 -
Frontiers in Pharmacology 2022We conducted a phase I bioequivalence trial in healthy Chinese subjects in the fasting and postprandial states. The goal of this trial was to compare the...
We conducted a phase I bioequivalence trial in healthy Chinese subjects in the fasting and postprandial states. The goal of this trial was to compare the pharmacokinetics and safety of the test preparation Cefaclor granule (Disha Pharmaceutical Group Co., Ltd.) and the reference preparation Cefaclor suspension (Ceclor, Eli Lilly and Company). In this trial, 24 subjects were selected in the fasting and postprandial states, respectively. Enrolled subjects randomly accepted a single dose of 0.125 g Cefaclor granule or Cefaclor suspension. The washout period was set as 2 days. Blood samples were collected within 8 h after administration in the fasting state and within 10 h after administration in the postprandial state. Plasma concentrations were determined by Liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters (AUC, C) were used to evaluate bioequivalence of the two drugs. In the fasting trial, the geometric mean ratios (90% confidence intervals CIs) for C, AUC, and AUC were 93.01% (85.96%-100.63%), 97.92% (96.49%-99.38%) and 97.95% (96.52%-99.41%), respectively. The GMR (90% CIs) for C, AUC, and AUC in postprandial state were 89.27% (81.97%-97.22%), 97.31% (95.98%-98.65%) and 97.31% (95.93%-98.71%), respectively. The 90% CIs of AUC and C in the fasting and postprandial states were within the 80-125% bioequivalence range. Therefore, Cefaclor granule and Cefaclor suspension were bioequivalent and displayed similar safety profiles. Furthermore, food intake affected the pharmacokinetic parameters of both drugs.
PubMed: 36278160
DOI: 10.3389/fphar.2022.1012294